Int J Biol Sci 2022; 18(9):3576-3591. doi:10.7150/ijbs.68216 This issue

Research Paper

Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma

Jing Li1,2*, Tao Yang3*, Qihong Wang4*, Yuedan Li5, Haiyan Wu1,6,7, Mei Zhang8, Hong Qi9, Hongxin Zhang3,10✉, Jinfeng Li1,6✉

1. Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98West 5th Road, Xi'an, Shaanxi 710004, China.
2. Department of Stomatology, Shaanxi Provincial Hospital, Xi'an, Shaanxi, 710038, China.
3. Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
4. Clinical Medical Research Center, The 75 th Group Army Hospital, Dali 671000, China.
5. Department of Pharmacy, General Hospital of Central Theater Command, Wuhan 430010, China.
6. Department of Cleft Palate-Craniofacial Surgery, College of Stomatology, Xi'an Jiaotong University, 98West 5th Road, Xi'an, Shaanxi 710004, China
7. Lianhu clinic, Affiliated Stomatological Hospital of Xi'an Jiaotong University, Xi'an, 710003, China.
8. Department of Ultrasound Diagnosis, Laoshan branch of NO.971 Hospital of the people's liberation army navy, Qingdao 266100, China.
9. Department of Pathology, Xi'an Jiaotong University College of Stomatology, 98West 5th Road, Xi'an, Shaanxi 710004, China.
10. Department of Intervention Therapy, The Second Affiliated Hospital, Shaanxi University of Traditional Chinese Medicine, Xianyang 712046, China.
*These authors equally contribute to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Li J, Yang T, Wang Q, Li Y, Wu H, Zhang M, Qi H, Zhang H, Li J. Upregulation of SQLE Contributes to Poor Survival in Head and Neck Squamous Cell Carcinoma. Int J Biol Sci 2022; 18(9):3576-3591. doi:10.7150/ijbs.68216. Available from https://www.ijbs.com/v18p3576.htm

File import instruction

Abstract

Graphic abstract

Recently, increasing attention has been paid to the role of Squalene epoxidase (SQLE) in several types of cancers. However, its functional role in tumor progression of head and neck squamous cell carcinoma (HNSCC) is still unclear. We performed bioinformatic analyses and relative experiments to assess the potential mechanism of SQLE-mediated HNSCC malignancy. And the results showed that SQLE was significantly upregulated in tumor samples compared with peritumor samples. Mechanistically, miR-584-5p downregulation may lead to the upregulation of SQLE in HNSCC. Moreover, high SQLE expression in HNSCC was associated with TNM stage, distant metastasis, and poor survival, indicating that SQLE be involved in the progression of HNSCC. Furtherly, SQLE boosted proliferation, migration, invasion of HNSCC cells in vitro and in vivo. Bioinformatic studies showed that PI3K/Akt signaling participated in HNSCC progression mediated by SQLE overexpression, which is confirmed by in vitro and in vivo analysis. Particularly, treatment with terbinafine, an inhibitor of SQLE widely used in the treatment of fungal infections, showed a therapeutic influence on HNSCC. Our findings demonstrate that SQLE plays a vital role in HNSCC progression, providing research evidence for SQLE as a prospective HNSCC therapeutic target and for terbinafine as a candidate drug of HNSCC treatment in the future

Keywords: SQLE, HNSCC, tumor progression, prognosis, terbinafine